公开(公告)号：WO2007061661A2

公开(公告)日：2007-05-31

申请号：PCT/US2006043951

申请日：2006-11-13

Applicant: AMGEN INC ,  BIOVITRUM AB ,  HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC A ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHRISTOPHER ,  ST JEAN DAVID J JR ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBEGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J ,  MARSHALL TERESA L

Inventor： HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC A ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHRISTOPHER ,  ST JEAN DAVID J JR ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBEGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J ,  MARSHALL TERESA L

IPC: C07D277/54 ,  A61K31/426 ,  A61K31/427 ,  C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14

CPC classification number: C07D277/54 ,  C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14

Abstract: The present invention relates to thiazolinones and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-ß-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11- ß-hydroxysteroid dehydrogenase type 1 enzyme.

Abstract translation: 本发明涉及噻唑啉酮以及包含该化合物的药物组合物，以及该化合物用于治疗与人类11-羟基类固醇脱氢酶1型酶有关的病症的用途的方法以及用于制备作用于 人类11-羟基类固醇脱氢酶1型酶。

公开(公告)号：WO2010008729A2

公开(公告)日：2010-01-21

申请号：PCT/US2009/047469

申请日：2009-06-16

Applicant: AMGEN INC. ,  MONIZ, George A. ,  FRIZZLE, Matthew J. ,  BERNARD, Charles ,  MARTINELLI, Michael ,  FAUL, Margaret ,  LARROW, Jay ,  HANSEN, Karl B. ,  KLINGENSMITH, Liane

Inventor： MONIZ, George A. ,  FRIZZLE, Matthew J. ,  BERNARD, Charles ,  MARTINELLI, Michael ,  FAUL, Margaret ,  LARROW, Jay ,  HANSEN, Karl B. ,  KLINGENSMITH, Liane

IPC: C07D277/14

CPC classification number: C07D277/54 ,  C07D263/48 ,  C07D277/42

Abstract: The present invention relates to methods of making compounds that inhibit 11-β-hydroxysteroid dehydrogenase type 1 enzyme (11-β HSD1). One method comprises (a) contacting a compound of formula (II) with a chiral base, deprotonating agent, and an alkylating agent R 3 -LG, (b) contacting the product of (a) with an acid to form a salt, and (c) reacting the salt with a base to form the compound of formula (I); wherein Z, R 1 , R 2 , and R 3 are defined herein.

Abstract translation: 本发明涉及制备抑制11-β-羟基类固醇脱氢酶1型酶（11-HSD1）的化合物的方法。 一种方法包括（a）使式（II）化合物与手性碱，去质子化剂和烷基化剂R3-LG接触，（b）使（a）的产物与酸形成盐，和 c）使所述盐与碱反应以形成式（I）化合物; 其中Z，R 1，R 2和R 3在本文中定义。

公开(公告)号：WO2005116002A2

公开(公告)日：2005-12-08

申请号：PCT/US2005018081

申请日：2005-05-24

Applicant: AMGEN INC ,  BIOVITRUM AB ,  HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHIRSTOPHER ,  ST JEAN DAVID ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBERGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J

Inventor： HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHIRSTOPHER ,  ST JEAN DAVID ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBERGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J

IPC: A61K31/42 ,  A61K31/426 ,  A61P3/00 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P19/10 ,  A61P25/24 ,  A61P25/28 ,  A61P29/00 ,  A61P31/12 ,  C07D20060101 ,  C07D263/48 ,  C07D277/42 ,  C07D277/54 ,  C07D277/60 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D513/10 ,  C07F7/18

CPC classification number: C07D417/06 ,  C07D263/34 ,  C07D263/48 ,  C07D275/03 ,  C07D277/42 ,  C07D277/54 ,  C07D277/60 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D513/10 ,  C07F7/1856

Abstract: The present invention relates to compounds with the formula (I), (II), (III) or (IV): (I) (II), (III), or (IV), wherein R , R , R , R , R , R , R , X and Z are as defined herein, and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-beta-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11-beta-hydroxysteroid dehydrogenase type 1 enzyme.

Abstract translation: 本发明涉及具有式（I），（II），（III）或（IV）：（I）（II），（III）或（IV））的化合物，其中R 1，R 2 R 3，R 4，R 5，R 6，R 7，X 7和Z如本文所定义，并且还涉及包含该化合物的药物组合物，以及使用方法 的用于治疗与人类11-β-羟基类固醇脱氢酶1型酶相关的疾病的化合物和用于制备作用于人类11-β-羟基类固醇脱氢酶1型酶的药物。

公开(公告)号：WO2007061661A3

公开(公告)日：2008-12-11

申请号：PCT/US2006043951

申请日：2006-11-13

Applicant: AMGEN INC ,  BIOVITRUM AB ,  HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC A ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHRISTOPHER ,  ST JEAN DAVID J JR ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBEGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J ,  MARSHALL TERESA L

Inventor： HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC A ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHRISTOPHER ,  ST JEAN DAVID J JR ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBEGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J ,  MARSHALL TERESA L

IPC: C07D277/54 ,  A61K31/426 ,  A61K31/427 ,  A61K31/428 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P9/12 ,  A61P19/10 ,  A61P25/24 ,  C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14

CPC classification number: C07D277/54 ,  C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14

Abstract: The present invention relates to thiazolinones and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-ß-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11- ß-hydroxysteroid dehydrogenase type 1 enzyme.

Abstract translation: 本发明涉及噻唑啉酮以及包含该化合物的药物组合物，以及该化合物用于治疗与人类11-羟基类固醇脱氢酶1型酶有关的病症的用途的方法以及用于制备作用于 人类11-羟基类固醇脱氢酶1型酶。

公开(公告)号：WO2007061661A4

公开(公告)日：2007-05-31

申请号：PCT/US2006/043951

申请日：2006-11-13

Applicant: AMGEN INC. ,  BIOVITRUM AB ,  HENRIKSSON, Martin ,  HOMAN, Evert ,  JOHANSSON, Lars ,  VALLGARDA, Jerk ,  WILLIAMS, Meredith ,  BERCOT, Eric, A. ,  FOTSCH, Christopher, H. ,  LI, Aiwen ,  CAI, Guolin ,  HUNGATE, Randall, W. ,  YUAN, Chester, Chenguang ,  TEGLEY, Christopher ,  ST. JEAN, David, J., Jr. ,  HAN, Nianhe ,  HUANG, Qi ,  LIU, Qingyian ,  BARTBEGER, Michael, D. ,  MONIZ, George, A. ,  FRIZZLE, Matthew, J. ,  MARSHALL, Teresa, L.

Inventor： HENRIKSSON, Martin ,  HOMAN, Evert ,  JOHANSSON, Lars ,  VALLGARDA, Jerk ,  WILLIAMS, Meredith ,  BERCOT, Eric, A. ,  FOTSCH, Christopher, H. ,  LI, Aiwen ,  CAI, Guolin ,  HUNGATE, Randall, W. ,  YUAN, Chester, Chenguang ,  TEGLEY, Christopher ,  ST. JEAN, David, J., Jr. ,  HAN, Nianhe ,  HUANG, Qi ,  LIU, Qingyian ,  BARTBEGER, Michael, D. ,  MONIZ, George, A. ,  FRIZZLE, Matthew, J. ,  MARSHALL, Teresa, L.

IPC: C07D277/54 ,  C07D277/60 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  A61K31/426 ,  A61K31/427 ,  A61K31/428 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P19/10 ,  A61P25/24 ,  A61P9/12

Abstract: The present invention relates to thiazolinones and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-β-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11- β-hydroxysteroid dehydrogenase type 1 enzyme.

公开(公告)号：WO2005116002B1

公开(公告)日：2006-08-24

申请号：PCT/US2005018081

申请日：2005-05-24

Applicant: AMGEN INC ,  BIOVITRUM AB ,  HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHIRSTOPHER ,  ST JEAN DAVID ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBERGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J

Inventor： HENRIKSSON MARTIN ,  HOMAN EVERT ,  JOHANSSON LARS ,  VALLGARDA JERK ,  WILLIAMS MEREDITH ,  BERCOT ERIC ,  FOTSCH CHRISTOPHER H ,  LI AIWEN ,  CAI GUOLIN ,  HUNGATE RANDALL W ,  YUAN CHESTER CHENGUANG ,  TEGLEY CHIRSTOPHER ,  ST JEAN DAVID ,  HAN NIANHE ,  HUANG QI ,  LIU QINGYIAN ,  BARTBERGER MICHAEL D ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J

IPC: C07D277/54 ,  A61K31/42 ,  A61K31/426 ,  A61P3/00 ,  A61P3/04 ,  A61P3/06 ,  A61P3/10 ,  A61P19/10 ,  A61P25/24 ,  A61P25/28 ,  A61P29/00 ,  A61P31/12 ,  C07D20060101 ,  C07D263/48 ,  C07D277/42 ,  C07D277/60 ,  C07D413/14 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D513/10 ,  C07F7/18

CPC classification number: C07D417/06 ,  C07D263/34 ,  C07D263/48 ,  C07D275/03 ,  C07D277/42 ,  C07D277/54 ,  C07D277/60 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D513/10 ,  C07F7/1856

Abstract: The present invention relates to compounds with the formula (I), (II), (III) or (IV): (I) (II), (III), or (IV), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X and Z are as defined herein, and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-ß-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11-ß-hydroxysteroid dehydrogenase type 1 enzyme.

Abstract translation: （I），（II），（III）或（IV）的化合物：其中R 1， R 2，R 3，R 4，R 5，R 6，R 6，R 5，R 8，R 8，R 8， R 7，X和Z如本文所定义，并且还涉及包含所述化合物的药物组合物，以及所述化合物用于治疗与人11-β-羟基类固醇相关的病症的方法 脱氢酶1型酶和用于制备作用于人类11-β-羟基类固醇脱氢酶1型酶的药物的用途。

公开(公告)号：WO2010008729A3

公开(公告)日：2010-05-06

申请号：PCT/US2009047469

申请日：2009-06-16

Applicant: AMGEN INC ,  MONIZ GEORGE A ,  FRIZZLE MATTHEW J ,  BERNARD CHARLES ,  MARTINELLI MICHAEL ,  FAUL MARGARET ,  LARROW JAY ,  HANSEN KARL B ,  KLINGENSMITH LIANE

Inventor： MONIZ GEORGE A ,  FRIZZLE MATTHEW J ,  BERNARD CHARLES ,  MARTINELLI MICHAEL ,  FAUL MARGARET ,  LARROW JAY ,  HANSEN KARL B ,  KLINGENSMITH LIANE

IPC: C07D277/42

CPC classification number: C07D277/54 ,  C07D263/48 ,  C07D277/42

Abstract: The present invention relates to methods of making compounds that inhibit 11-ß-hydroxysteroid dehydrogenase type 1 enzyme (11-ß HSD1). One method comprises (a) contacting a compound of formula (II) with a chiral base, deprotonating agent, and an alkylating agent R3-LG, (b) contacting the product of (a) with an acid to form a salt, and (c) reacting the salt with a base to form the compound of formula (I); wherein Z, R1, R2, and R3 are defined herein.

Abstract translation: 本发明涉及制备抑制11-β-羟基类固醇脱氢酶1型酶（11-HSD1）的化合物的方法。 一种方法包括：（a）使式（II）的化合物与手性碱，去质子化剂和烷基化剂R 3 -LG接触，（b）使（a）的产物与酸接触以形成盐，和 c）使该盐与碱反应以形成式（I）的化合物; 其中Z，R 1，R 2和R 3如本文所定义。

公开(公告)号：WO2009002445A1

公开(公告)日：2008-12-31

申请号：PCT/US2008/007682

申请日：2008-06-20

Applicant: AMGEN INC. ,  MONIZ, George A. ,  FRIZZLE, Matthew J. ,  BERNARD, Charles ,  MARTINELLI, Michael ,  FAUL, Margaret ,  NANI, Roger ,  LARROW, Jay

Inventor： MONIZ, George A. ,  FRIZZLE, Matthew J. ,  BERNARD, Charles ,  MARTINELLI, Michael ,  FAUL, Margaret ,  NANI, Roger ,  LARROW, Jay

IPC: C07D277/42

CPC classification number: C07D277/42

Abstract: ABSTRACT The present invention relates to methods of making compounds that inhibit 11- -hydroxysteroid dehydrogenase type 1 enzyme (11- HSD1). One method comprises (a) contacting a compound of formula (II) sequentially with a chiral base in the presence of an amine, and an alkylating agent R3-LG, (b) contacting the product of (a) with an acid to form a salt, and (c) reacting the salt with a base to form the compound of formula (I). wherein Z, R1, R2, and R3 are defined herein.

Abstract translation: 摘要本发明涉及制备抑制11-羟基类固醇脱氢酶1型（11-HSD1）的化合物的方法。 一种方法包括（a）在胺的存在下将式（II）化合物与手性碱顺序接触，和烷基化试剂R3-LG，（b）使（a）的产物与酸反应形成 盐，和（c）使盐与碱反应以形成式（I）化合物。 其中Z，R 1，R 2和R 3在本文中定义。

公开(公告)号：WO2005116002A3

公开(公告)日：2005-12-08

申请号：PCT/US2005/018081

申请日：2005-05-24

Applicant: AMGEN INC. ,  BIOVITRUM AB ,  HENRIKSSON, Martin ,  HOMAN, Evert ,  JOHANSSON, Lars ,  VALLGARDA, Jerk ,  WILLIAMS, Meredith ,  BERCOT, Eric ,  FOTSCH, Christopher, H. ,  LI, Aiwen ,  CAI, Guolin ,  HUNGATE, Randall, W. ,  YUAN, Chester, Chenguang ,  TEGLEY, Chirstopher ,  ST. JEAN, David ,  HAN, Nianhe ,  HUANG, Qi ,  LIU, Qingyian ,  BARTBERGER, Michael, D. ,  MONIZ, George, A. ,  FRIZZLE, Matthew, J.

Inventor： HENRIKSSON, Martin ,  HOMAN, Evert ,  JOHANSSON, Lars ,  VALLGARDA, Jerk ,  WILLIAMS, Meredith ,  BERCOT, Eric ,  FOTSCH, Christopher, H. ,  LI, Aiwen ,  CAI, Guolin ,  HUNGATE, Randall, W. ,  YUAN, Chester, Chenguang ,  TEGLEY, Chirstopher ,  ST. JEAN, David ,  HAN, Nianhe ,  HUANG, Qi ,  LIU, Qingyian ,  BARTBERGER, Michael, D. ,  MONIZ, George, A. ,  FRIZZLE, Matthew, J.

IPC: C07D277/54 ,  C07D263/48 ,  A61K31/42 ,  A61K31/426 ,  A61P3/04 ,  A61P3/00 ,  A61P3/06 ,  A61P3/10 ,  A61P19/10 ,  A61P31/12 ,  A61P29/00 ,  A61P25/28 ,  A61P25/24

Abstract: The present invention relates to compounds with the formula (I), (II), (III) or (IV): (I) (II), (III), or (IV), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X and Z are as defined herein, and also to pharmaceutical compositions comprising the compounds, as well as methods of use of the compounds for treatment of disorders associated with human 11-β-hydroxysteroid dehydrogenase type 1 enzyme and for the preparation of a medicament which acts on the human 11-β-hydroxysteroid dehydrogenase type 1 enzyme.